Long-term Opioid Use a Risk Factor for Cancer

Abdullah Hashmi, MD, for Medscape

April 12, 2022

The study covered in this summary was published in papers.ssrn.com as a preprint and has not yet been peer-reviewed.

Key Takeaways

  • Patients with a history of long-term opioid use for chronic pain have an elevated risk for cancer, according to this propensity-score-matched, population-based cohort study.

  • Specifically, the incidence rate ratio for lung, colorectal, breast, prostate, head and neck, pancreatic, gastric, esophageal, and ovarian cancers and for hepatocellular carcinoma were higher in patients with than without a history of long-term opioid use.

Why This Matters

  • Although long-term opioid use has been associated with poor survival outcomes in cancer patients, this is the largest head-to-head propensity-score-matched study to investigate long-term opioid use with an opioid washout interval before cancer diagnosis.

  • It is also the first study to report incidence rates and incidence rate ratios for common cancers in patients with and without a history of long-term opioid use.

  • The findings can be used as a reference for establishing health policies and to suggest that alternative analgesia might reduce cancer risk.

Study Design

  • Patients older than 20 years with a diagnosis of chronic pain from January 2008 to December 2009 were identified from the Taiwan National Health Insurance Research Database. Propensity scoring was used to match, in a 4:1 ratio, 50,888 patients with a history of long-term opioid use with 12,722 patients without.

  • In the long-term group, patients used opioids most days for more than 3 months and had a mean annual opioid dose of more than 180 defined daily doses. In the nonopioid control group, the annual daily doses were zero. For all patients, the opioid washout period was at least 2 years.

  • Patients were excluded from the study if they had received a cancer diagnosis during that 2-year opioid washout period or if they had a diagnosis of opioid abuse.

  • Primary endpoints were the incidence rates and incidence rate ratios of cancer in the two groups.

Key Results

  • There were no notable differences in demographic characteristics, medical history, or social history between the two groups.

  • The difference in crude cancer incidence between the opioid group and the control group was significant (P < .001).

  • On multivariate Cox regression analysis, the adjusted hazard ratio was 2.66 for the opioid group compared with the control group (P < .001).

  • Long-term opioid use was shown to be a risk for these cancers: lung (incidence rate ratio [IRR],1.87), hepatocellular carcinoma (IRR, 1.97), colorectal (IRR, 2.39), breast (IRR, 2.43), prostate (IRR, 2.00), head and neck (IRR, 1.79), pancreatic (IRR, 1.87), gastric (IRR, 2.43), esophageal (IRR, 2.43), and ovarian (IRR, 2.33).


  • Patients in the study cohort were of Asian ethnicity, so results cannot be generalized to non-Asian populations.

  • Diagnoses of comorbid conditions were based on ICD-9-CM or ICD-10-CM codes in the database, and therefore not verified.

  • The overall incidence of cancer might have been higher in the opioid group if the mortality rate had been lower.

  • The database did not contain information on the dietary habits of patients, which could have affected cancer risk.


  • The study received no commercial funding.

  • None of the authors disclosed relevant financial relationships.

This is a summary of a preprint research study, Impact of Long-term Opioid Use on Cancer Risk in Patients With Chronic Pain, written by researchers from the Department of Anesthesiology at Zhengzhou University in Henan, China, and from the Center for Regional Anesthesia and Pain Medicine, Taipei Medical University, Taiwan, published on Preprints with the Lancet and provided to you by Medscape. This study has not yet been peer-reviewed. The full text of the study can be found on papers.ssrn.com.


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